Context Supplemental methotrexate (MTX) may affect the clinical course of Graves’ disease (GD). Objective To evaluate the efficacy of add-on MTX on medical treatment in GD. Design Prospective, open-label, randomized supplementation controlled trial. Setting Academic endocrine outpatient clinic. Patients One hundred fifty-three untreated hyperthyroid patients with GD. Intervention Patients received MTX 10 mg/d with methimazole (MMI) or MMI only. MTX and MMI were discontinued at months 12 to 18 in euthyroid patients. Main Outcome Measures Discontinuation rate at month 18 in each group. Results In the MTX with MMI group, the discontinuation rate was higher than the MMI group at months 15 to 18 [50.0 vs 33.3%, P = .043, 95% confidence interval (CI) 1.020-3.922; and 55.6 vs 38.9%, P = .045, 95% CI 1.011-3.815, respectively). The decrease in thyrotropin-related antibodies (TRAb) levels in the MTX with MMI group was significant from baseline to month 6 compared to the MMI alone group [MTX + MMI 67.22% (43.12-80.32), MMI 54.85% (33.18-73.76), P = .039] and became more significant from month 9 [MTX + MMI 77.79% (62.27-88.18), MMI 69.55% (50.50-83.22), P = .035] to month 18 (P < .01 in 15-18 months). A statistically significant difference was seen between the levels of TRAb in the MTX with MMI group and the MMI group at 9 to 18 months. There were no significant differences in the levels of free T3, free T4, and TSH between the 2 groups. No serious drug-related adverse events were observed in either group (P = .771). Conclusion Supplemental MTX with MMI resulted in a higher discontinuation rate and improvement in decreased TRAb levels to homeostatic levels faster than methimazole treatment alone at months 12 to 18.

Context: Thyroid-stimulating immunoglobulin (TSI) and thyrotropin receptor antibody (TRAb) are specific biomarkers for Graves disease (GD), but their clinical characteristics are not fully understood. Objective: To clarify the clinical features and prognostic significance of TSI and TRAb in patients with GD. Methods: We conducted a retrospective data analysis and a follow-up study. Medical records of patients newly diagnosed with GD were examined. TSI and TRAb correlations were assessed using Passing-Bablok regression and Bland-Altman plot. Patients were categorized into unresolved (Group A) and resolved (Group B) hyperthyroidism based on thyroid function after 1 month of therapy. The relationship between thyroid function and changes in TRAb and TSI was analyzed. Logistic regression identified relapse risk factors, including TSI levels at antithyroid drugs (ATDs) withdrawal in the follow-up study. Results: Data from 957 patients (762 female and 195 male) revealed a strong correlation between TRAb and TSI (r = 0.873, P < .001). Compared to group B, group A showed minimal antibody decline (100% [interquartile range (IQR) 87.91%-115.1%] and 100% [IQR 85.03%-118.3%], respectively). Among 206 patients followed for over 12 months after ATD discontinuation, the relapse rate was 41.26%. Relapse was more frequent in patients with positive TSI (54.84% vs 35.42%, P < .05). Positive TSI levels at withdrawal, past history of GD, age, and mild thyroid-associated ophthalmopathy were independent relapse predictors. Conclusion: TSI and TRAb are strongly correlated in GD, with slow antibody decline linked to unresolved hyperthyroidism. Discontinuing ATDs may be considered when both TSI and TRAb are negative.

Thyroid carcinoma (THCA) ranks among the most prevalent cancers globally. Integrating advanced genomic and proteomic analyses to construct a protein-based prognostic model promises to identify effective biomarkers and explore new therapeutic avenues. In this study, proteomic data from The Cancer Proteomics Atlas (TCPA) and clinical data from The Cancer Genome Atlas (TCGA) were utilized. Using Kaplan–Meier, Cox regression, and LASSO penalized Cox analyses, we developed a prognostic risk model comprising 13 proteins (S100A4, PAI1, IGFBP2, RICTOR, B7-H3, COLLAGENVI, PAR, SNAIL, FAK, Connexin-43, Rheb, EVI1, and P90RSK_pT359S363). The protein prognostic model was validated as an independent predictor of survival time in THCA patients, based on risk curves, survival analysis, receiver operating characteristic curves and independent prognostic analysis. Additionally, we explored the immune cell infiltration and tumor mutational burden (TMB) related to these features. Notably, our study proved a novel approach for predicting treatment responses in THCA patients, including those undergoing chemotherapy and targeted therapy.